| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg | |||
| 50mg | |||
| Other Sizes |
| Targets |
CDK9
CDK9 (cyclin-dependent kinase 9). TP-1287 is a prodrug that is converted to alvocidib, which inhibits CDK9. CDK9 inhibition leads to reduced RNA polymerase II-mediated transcription and downregulation of short-lived anti-apoptotic proteins such as MCL-1. |
|---|---|
| ln Vitro |
TP-1287 inhibits RNA polymerase II-mediated CDK9-mediated MCL-1 expression [1].
TP-1287 inhibits RNA polymerase II-mediated CDK9-mediated MCL-1 expression. As a prodrug, it is converted to the active parent compound alvocidib in cells. Alvocidib is a potent CDK9 inhibitor with antiproliferative activity against various cancer cell lines. |
| ln Vivo |
In multiple myeloma models, TP-1287 (2.5–15 mg/kg; oral) suppresses the growth of tumors [1]. After oral dosing, TP-1287 is effectively metabolized in vivo to the parent drug and is highly soluble over a wider pH range than Alvocidib (HY-10005) [2].
TP-1287 (2.5-15 mg/kg; oral) suppresses tumor growth in models of multiple myeloma. It is highly soluble over a broader pH range than alvocidib and is efficiently metabolized to the parent compound in vivo following oral administration. |
| Enzyme Assay |
As a prodrug, TP-1287 is converted to alvocidib in vivo. CDK9 inhibition is measured using kinase assays with purified CDK9/cyclin T1 enzyme. Alvocidib binding to CDK9 is assessed by measuring ATP competition or using fluorescently labeled probes.
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| Cell Assay |
Cell viability is assessed in multiple myeloma and other cancer cell lines treated with TP-1287 or alvocidib using MTT or CellTiter-Glo assays. MCL-1 protein levels are measured by Western blot. RNA polymerase II phosphorylation is assessed to monitor CDK9 inhibition.
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| Animal Protocol |
Animal/Disease Models: RPMI-8226 xenograft model for multiple myeloma[1]
Doses: 2.5, 7.5, and 15 mg/kg Route of Administration: Oral Experimental Results: Achieved tumor growth Inhibition (%TGI) of 56.0, 76.6, and 93.9% at doses of 2.5, 7.5, and 15 mg/kg, respectively. Mouse xenograft models of multiple myeloma are administered TP-1287 orally at 2.5-15 mg/kg. Tumor growth is monitored, and pharmacodynamic markers (MCL-1, phospho-RNA polymerase II) are assessed in tumor tissues. |
| ADME/Pharmacokinetics |
TP-1287 has a molecular weight of 481.82 and a molecular formula of C21H21ClNO₈P. It is highly soluble over a broader pH range than alvocidib. It is efficiently metabolized to alvocidib in vivo following oral administration.
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| Toxicity/Toxicokinetics |
No detailed toxicity data has been published for TP-1287. As an investigational compound, its safety profile is being evaluated in clinical trials. Prodrug design may improve oral bioavailability and reduce gastrointestinal toxicity compared to alvocidib.
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| References | |
| Additional Infomation |
TP-1287 is a clinical-stage, orally bioavailable phosphate prodrug of the potent CDK9 inhibitor alvocidib (flavopiridol). It has been evaluated in clinical trials for multiple myeloma and other cancers. It is designed to improve oral bioavailability and solubility compared to alvocidib.
|
| Exact Mass |
481.07
|
|---|---|
| Elemental Analysis |
C, 52.35; H, 4.39; Cl, 7.36; N, 2.91; O, 26.56; P, 6.43
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| CAS # |
2044686-42-0
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| PubChem CID |
124083048
|
| Appearance |
Light yellow to yellow solid powder
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
4
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| Heavy Atom Count |
32
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| Complexity |
790
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| Defined Atom Stereocenter Count |
2
|
| InChi Key |
YRNFLVUMZIRYKY-BLLLJJGKSA-N
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| InChi Code |
InChI=1S/C21H21ClNO8P/c1-23-7-6-12(16(26)10-23)19-18(31-32(27,28)29)9-15(25)20-14(24)8-17(30-21(19)20)11-4-2-3-5-13(11)22/h2-5,8-9,12,16,25-26H,6-7,10H2,1H3,(H2,27,28,29)/t12-,16+/m0/s1
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| Chemical Name |
2-(2-chlorophenyl)-5-hydroxy-8-((3S,4R)-3-hydroxy-1-methylpiperidin-4-yl)-4-oxo-4H-chromen-7-yl dihydrogen phosphate
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| Synonyms |
TP 1287; TP-1287; TP1287; alvocidib prodrug;
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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